Serum Amyloid A and the Acute Phase Response in Bovine Pneumonic Pasteurellosis

Horadagoda, Ajantha (1994) Serum Amyloid A and the Acute Phase Response in Bovine Pneumonic Pasteurellosis. PhD thesis, University of Glasgow.

Abstract

The acute phase response is a cascade of events which occurs immediately after an injury or infection. It is a non-specific, non-immune defence mechanism which consists of a local and a systemic response that vary from species to species. The aim of the work described here was to increase our understanding of the systemic acute phase response (APR) in cattle. An established experimental model for bovine pneumonic pasteurellosis in which calves were inoculated intra-tracheally with P. haemolytica A1 or with lipopolysaccharide (LPS) extracted from the organism was used in these studies of the APR. Serum amyloid A (SAA), a major acute phase protein in cattle was monitored in an indirect enzyme-linked immunosorbent assay developed using a commercially available rabbit anti-human SAA antibody. The assay was standardized using a pool of acute phase bovine serum which was quantified with purified bovine SAA (b-SAA) prepared by hydrophobic interaction chromatography and gel filtration. This allowed b-SAA concentrations in serum to be estimated in SI units with the detection limit of the assay being 3mug ml-1. The APR induced with P. haemolytica was characterised within 24 hours by the clinical signs of fever, anorexia, tachypnoea and a dull demeanour and was associated with a marked neutrophilic leukocytosis, hypoferraemia and hypozincaemia. During the same period the endocrine system was affected with an elevation of cortisol and a reduction of thyroxine being detected. The acute phase protein response was manifested by an increase in both SAA and haptoglobin (Hp) concentrations within 24 hours of inoculation and the concentration of both proteins reached a peak at 48 hours post inoculation. However, in studies comparing the effect of different isolates of P. haemolytica, on the acute phase protein response only the SAA levels correlated with the pathogenicity of the infectious organism. Frequent sampling during the initial phase of the APR indicated an earlier rise in SAA compared to Hp. In addition, a rise in fibrinogen was found at 24 hours, but there were no clear increases in ceruloplasmin or copper concentrations. Most results from a comprehensive biochemical analysis of sera from infected animals were within the normal range, but plasma concentration of bilirubin was increased and glutamate dehydrogenase activity was decreased. Animals treated with P. haemolytica LPS intra-venously demonstrated an APR which was comparable to that observed when the whole organism was challenged intra-tracheally. In studies to determine the role of bovine cytokines in the infection, both P. haemolytica and LPS elicited a tumour necrosis factor (TNFalpha) response which peaked 2 hours after challenge and returned to non- detectable levels after a further 4 hours. Unsuccessful attempts were made to measure the plasma concentration of Interleukin 1 and Interleukin 6. It is concluded that the APR in bovine pneumonic pasteurellosis is characterised by clinical changes and a wide array of pathophysiological alterations which include leukocytosis, mineral redistribution, endocrine and metabolic changes, and an acute phase protein response. The APR varied with the isolate of P. haemolytica and appears to correlate with the pathogenicity of the organism. Furthermore, the marked response in TNFalpha concentrations implicates this cytokine as a major mediator of the APR in cattle.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: David Eckersall
• Keywords: Veterinary science, Animal diseases
• Date of Award: 1994
• Depositing User: Enlighten Team
• Unique ID: glathesis:1994-75340
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 20:38
• Last Modified: 19 Nov 2019 20:38
• URI: https://theses.gla.ac.uk/id/eprint/75340